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Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection.

Farzan M, Choe H, Martin K, Marcon L, Hofmann W, Karlsson G, Sun Y, Barrett P, Marchand N, Sullivan N, Gerard N, Gerard C, Sodroski J - J. Exp. Med. (1997)

Bottom Line: Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages.The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues.These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.

ABSTRACT
Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor, but no other receptors for these viruses have been identified. Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages. The more efficient of these, gpr15, is also expressed in human CD4(+) T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.

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Related in: MedlinePlus

An alignment of human gpr1, human gpr15, rhesus CCR5  (rccr5), and human CCR5 from the NH2-terminus through the first cysteine of CCR5 is shown. Tyrosines shown to be important for HIV-1  and SIVmac239 entry are shown in bold. Other residues similarly positioned in these proteins are underlined. Sequences for gpr1 and gpr15 are  provided in references 53 and 54, respectively.
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Figure 3: An alignment of human gpr1, human gpr15, rhesus CCR5 (rccr5), and human CCR5 from the NH2-terminus through the first cysteine of CCR5 is shown. Tyrosines shown to be important for HIV-1 and SIVmac239 entry are shown in bold. Other residues similarly positioned in these proteins are underlined. Sequences for gpr1 and gpr15 are provided in references 53 and 54, respectively.

Mentions: In primary structure, gpr1 and gpr15 resemble the angiotensin II receptor and the orphan receptors dez and apj more than they do any of the known chemokine receptors (53, 54). Gpr15, like dez and gpr1, lacks the cysteines in the NH2-terminal region and the third extracellular loop which, in the chemokine receptors, are thought to be disulfide linked. It is interesting that despite the general sequence divergence of gpr15/gpr1 and other identified primate immunodeficiency virus coreceptors the gpr15 and gpr1 amino termini contain three tyrosines which align with similarly positioned tyrosines in CCR5 (Fig. 3). Alteration of these tyrosines has been shown to decrease the efficiency with which CCR5 supports the entry of SIV and M-tropic HIV-1 isolates (Farzan, M., H. Choe, and J. Sodroski, unpublished observations). The identification of gpr15 and gpr1 as SIV coreceptors suggests a greater range and complexity of coreceptors for the primate immunodeficiency viruses than previously described. Comparative studies of these divergent coreceptors with the known coreceptors for these viruses should assist in the identification of common structural elements in 7-TMS proteins which serve as viral entry cofactors.


Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection.

Farzan M, Choe H, Martin K, Marcon L, Hofmann W, Karlsson G, Sun Y, Barrett P, Marchand N, Sullivan N, Gerard N, Gerard C, Sodroski J - J. Exp. Med. (1997)

An alignment of human gpr1, human gpr15, rhesus CCR5  (rccr5), and human CCR5 from the NH2-terminus through the first cysteine of CCR5 is shown. Tyrosines shown to be important for HIV-1  and SIVmac239 entry are shown in bold. Other residues similarly positioned in these proteins are underlined. Sequences for gpr1 and gpr15 are  provided in references 53 and 54, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198994&req=5

Figure 3: An alignment of human gpr1, human gpr15, rhesus CCR5 (rccr5), and human CCR5 from the NH2-terminus through the first cysteine of CCR5 is shown. Tyrosines shown to be important for HIV-1 and SIVmac239 entry are shown in bold. Other residues similarly positioned in these proteins are underlined. Sequences for gpr1 and gpr15 are provided in references 53 and 54, respectively.
Mentions: In primary structure, gpr1 and gpr15 resemble the angiotensin II receptor and the orphan receptors dez and apj more than they do any of the known chemokine receptors (53, 54). Gpr15, like dez and gpr1, lacks the cysteines in the NH2-terminal region and the third extracellular loop which, in the chemokine receptors, are thought to be disulfide linked. It is interesting that despite the general sequence divergence of gpr15/gpr1 and other identified primate immunodeficiency virus coreceptors the gpr15 and gpr1 amino termini contain three tyrosines which align with similarly positioned tyrosines in CCR5 (Fig. 3). Alteration of these tyrosines has been shown to decrease the efficiency with which CCR5 supports the entry of SIV and M-tropic HIV-1 isolates (Farzan, M., H. Choe, and J. Sodroski, unpublished observations). The identification of gpr15 and gpr1 as SIV coreceptors suggests a greater range and complexity of coreceptors for the primate immunodeficiency viruses than previously described. Comparative studies of these divergent coreceptors with the known coreceptors for these viruses should assist in the identification of common structural elements in 7-TMS proteins which serve as viral entry cofactors.

Bottom Line: Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages.The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues.These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.

ABSTRACT
Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor, but no other receptors for these viruses have been identified. Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages. The more efficient of these, gpr15, is also expressed in human CD4(+) T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.

Show MeSH
Related in: MedlinePlus